Intraluminal acid activates esophageal nodose C fibers after mast cell activation

Shizhong Zhang, Zhenyu Liu, Andrea Heldsinger, Chung Owyang, Shaoyong Yu

Research output: Contribution to journalArticle

Abstract

Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2-3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acidinduced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume306
Issue number3
DOIs
StatePublished - Feb 1 2014

Fingerprint

Unmyelinated Nerve Fibers
Mast Cells
Ovalbumin
Acids
Action Potentials
Herpes Zoster
Electric Impedance
Inhalation
Esophagus
Nodose Ganglion
Chemical Stimulation
Occludin
Tight Junction Proteins
Heartburn
Nociception
Nerve Endings
Capsaicin
Chest Pain
Guinea Pigs
Epithelium

Keywords

  • Acid
  • C fiber
  • Esophagus
  • Mast cell
  • Vagal afferent

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Intraluminal acid activates esophageal nodose C fibers after mast cell activation. / Zhang, Shizhong; Liu, Zhenyu; Heldsinger, Andrea; Owyang, Chung; Yu, Shaoyong.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 306, No. 3, 01.02.2014.

Research output: Contribution to journalArticle

@article{d1326e7fb5df471a9c0337e31117a25e,
title = "Intraluminal acid activates esophageal nodose C fibers after mast cell activation",
abstract = "Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2-3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acidinduced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation.",
keywords = "Acid, C fiber, Esophagus, Mast cell, Vagal afferent",
author = "Shizhong Zhang and Zhenyu Liu and Andrea Heldsinger and Chung Owyang and Shaoyong Yu",
year = "2014",
month = "2",
day = "1",
doi = "10.1152/ajpgi.00142.2013",
language = "English (US)",
volume = "306",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Intraluminal acid activates esophageal nodose C fibers after mast cell activation

AU - Zhang, Shizhong

AU - Liu, Zhenyu

AU - Heldsinger, Andrea

AU - Owyang, Chung

AU - Yu, Shaoyong

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2-3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acidinduced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation.

AB - Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2-3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acidinduced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation.

KW - Acid

KW - C fiber

KW - Esophagus

KW - Mast cell

KW - Vagal afferent

UR - http://www.scopus.com/inward/record.url?scp=84893399260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893399260&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00142.2013

DO - 10.1152/ajpgi.00142.2013

M3 - Article

VL - 306

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 3

ER -